Chromium trioxide

Endpoint summary

Description of key information

Positive results from in vivo corrosivity screening studies are available for chromium (VI) trioxide.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: corrosive

Effects on respiratory irritation: irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15th-18th February 1983

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Proprietary guideline-compliant study

Qualifier:

according to guideline

Guideline:

other: US Department of Transport

Deviations:

no

Principles of method if other than guideline:

Corrosivity screening test in the rabbit in vivo

GLP compliance:

no

Remarks:

Pre-GLP study

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

physiological saline

Controls:

not required

Amount / concentration applied:

0.5 g, moistened with 0.5 ml saline

Duration of treatment / exposure:

Up to 30 minutes

Observation period:

Up to 1 hour

Number of animals:

Two

Details on study design:

Two animals were exposed for three minutes and observed at regular intervals for corrosive effects.

Irritation parameter:

overall irritation score

Basis:

mean

Reversibility:

not reversible

Remarks on result:

other: signs of local tissue destruction

Irritant / corrosive response data:

Signs in both animals indicate local tissue destruction, which was confirmed by histopathology.

Other effects:

Histopathology showed coagulative necrosis of the epidermis and the outer dermis, with epidermal sloughing and capillary congestion.

Brown discoloration of the application site in the first animal after 3 minutes prevented the assessment of erythema; slight oedema (Grade 2) was apparent at this stage. Similar findings were noted at 15 minutes (following replacement of the patch). At 30 minutes Stage 3 oedema was observed and the animal showed signs of pain. The skin was noted to be hard and leathery. The animal was sacrificed at this point. The second animal showed signs of pain within 30 seconds of administration. Scoring of erythema was not possible after 3 minutes due to brown discoloration of the skin: the patch was not replaced at this point. Slight (Grade 2) oedema was apparent and the skin was hard. Moderate (Grade 3) oedema was seen at 30 and 60 minutes, at which point the animal was sacrificed.

Interpretation of results:

other: corrosive based on EU GHS criteria

Conclusions:

The results of the study show that chromium (VI) trioxide is corrosive to skin.

Executive summary:

0.5 g chromic acid (moistened with 0.5 ml physiological saline) was applied under occlusive conditions to the shorn dorsal skin of two rabbits. The application time in the first animal was 30 minutes; observations were made at up to 30 minutes, when the animal was sacrificed for humane reasons. Application time in the second animal was 3 minutes; observations were made for up to 1 hour, when the animal was sacrificed for humane reasons. In both animals, the skin at the application site appeared hard and brown, preventing the assessment of erythema. Oedema and pain were observed in both animals from early timepoints. Histopathology of skin at the application site confirmed a corrosive effect.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study reported in summary form only, but the results support the proposed classification.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

The method is a non-standard screening/prelimary eye and skin irritation study, but provides adequate information to support the proposed classification.

GLP compliance:

no

Remarks:

Study pre-dates GLP

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 3-4 kg
- Housing: individually

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

24 hours

Observation period:

Up to seven days

Number of animals:

Two

Details on study design:

TEST SITE
- Area of exposure: inner surface of ear

REMOVAL OF TEST SUBSTANCE
- Washing (if done): after exposure period the test item was washed off using water and soap
- Time after start of exposure: 24h

Irritation parameter:

other: pallor, desquamation and severe reddening

Basis:

mean

Time point:

7 d

Remarks on result:

probability of severe irritation

Irritant / corrosive response data:

Overall conclusion: severe skin irritant.

Other effects:

Signs of irritation including pallor, desquamation and severe reddening are reported. The summary also indicates that the administered dose (equivalent to 125-170 mg/kg bw) was lethal to the treated animals. This finding is discussed under the acute dermal toxicity section.

The results are not reported in detail but are consistent with the results of the other proprietary study and literature reports which indicate that chromium trioxide is a severe skin irritant.

Interpretation of results:

other: EU GHS criteria

Conclusions:

The results are not reported in great detail but are consistent with the results of other studies and literature reports which indicate that chromium trioxide is a severe skin irritant.

Executive summary:

Chromium trioxide (500 mg) applied to the skin of rabbits for 24 hours prodiuced severe irritation and lethality.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is reported in summary form only, but the results support the proposed classification

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study is a non-guideline irritation screening study.

GLP compliance:

no

Remarks:

Pre-dates GLP; screening study

Species:

rabbit

Strain:

New Zealand White

Vehicle:

unchanged (no vehicle)

Controls:

no

Duration of treatment / exposure:

Animals were exposed to 50 mg of the test material and observed for up to 7 days.

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

Two

Irritation parameter:

overall irritation score

Basis:

other: not applicable

Time point:

other: not applicable

Max. score:

100

Reversibility:

not reversible

Remarks on result:

other: An overall score irritation is not given in the report. A maximum score of 100 has been added for completeness. The test substance was found to be corrosive.

Irritant / corrosive response data:

An overall score irritation is not given in the report. A maximum score of 100 has been added for completeness. The test substance was found to be corrosive.

Other effects:

Very marked reddening and corrosion are noted.

Results are reported very briefly (very marked reddening and corrosive effects).

Interpretation of results:

other: EU GHS Cat. 1 cause serious eye damage

Conclusions:

The results of this study indicate that chromium trioxide is corrosive.

Executive summary:

50 mg chromium trioxide instilled into one eye of two New Zealand White rabbits produced corrosive effects.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

A corrosivity screen in the rabbit in vivo (Cuthbert, 1983) showed that chromic acid (aqueous chromium trioxide) is corrosive to the skin. The results of a briefly reported screening study (Thyssen, 1979) also indicate severe skin and irritation. The EU RAR (2005) does not include any studies but states that 'aqueous chromium (VI) trioxide is a corrosive substance due to its low pH'. Further testing in vivo for skin or eye irritation (i.e. in guideline and GLP-compliant studies) is therefore not required and is not justifiable both on scientific grounds or for reasons of animal welfare. The EU RAR (2005) states that symptoms of sensory irritation of the respiratory tract are known to occur among chrome plating workers exposed to a mist of aqueous chromium (VI) trioxide. Since this material is corrosive, such symptoms are to be expected. No quantitative data on such irritation are available from studies of workers.

Chromium trioxide is markedly more corrosive to skin than other water-soluble hexavalent chromium compounds, as a consequence of its low pH when mixed with water or moisture to form chromic acid. Read-across between chromium trioxide and other water-soluble hexavalent chromium compounds is therefore not appropriate for skin and eye irritation/corrosion.

Further available information on skin irritation

The EU RAR summarises the results of a number of non-standard studies in animals which indicate that the water-soluble Cr (VI) compounds sodium chromate, sodium dichromate and potassium dichromate are likely to be skin irritants. Experience from occupational exposure to these compounds indicates severe dermal irritation / corrosivity. The studies were performed in different species and using various non-standard methods. All of the water-soluble Cr (VI) compounds were found to be skin irritants in the studies sumamrised in this review. Chromium (VI) trioxide is considered to be corrosive as a consequence of its low pH.

Single application of sodium chromate, sodium dichromate or potassium dichromate to rabbit skin for 4 hours resulted in irritant responses of erythema and oedema of grade 3 or less when the compounds were in solution or moistened with saline. The reactions appeared to subside but irritation was still present at 6 days after application. In general, abrasion of the skin before treatment had no effect on the outcome. It was claimed in one study that single application of potassium dichromate solution to abraded skin in the guinea pig caused skin 'sores'.

In terms of human experience, direct accidental contact with very acidic or high temperature solutions of highly water-soluble Cr (VI) compounds has resulted in severe burns to human skin. It is not clear from the available reports whether intact skin is damaged by single contact with neutral solutions of such compounds. In one patch test study, some volunteers responded to 0.5% aqueous potassium dichromate with mild irritation, especially around the hair follicles.

Aqueous chromium (VI) trioxide is a corrosive substance due to its low pH. Concentration-dependent erythema was observed in guinea pigs when repeated applications were made daily for 4 days on unabraided skin using potassium dichromate solution. In another study in the guinea pig, daily repeated application up to 28 days resulted in a more severe response only when the skin was traumatised by wax

depilation or non-scarring abrasion prior to application. T he severity of response was dependent on the concentration of potassium dichromate and the degree of trauma to the skin. Chrome ulcers with thick

eschar and underlying tissue necrosis were observed. In workers regularly exposed to highly watersoluble Cr (VI) in solution, chrome ulcers develop after some initial damage to the skin. This has been described for dye workers handling sodium or potassium dichromate solutions and frequently in exposed workers in the chromate production and chrome plating industries. The severity of the ulcer depends upon the frequency and duration of skin contamination. Small papules develop initially, progressing to an ulcer which penetrates gradually to deeper skin layers. Typically, chrome ulcers have a hard circular periphery and a cavity leading to a base covered with exudate or a crust.

The findings of a number of non-standard studies in various animal species indicate that water-soluble Cr (VI) compounds sodium chromate, sodium dichromate and potassium dichromate are likely to be skin irritants

Further available information on eye irritation

The EU RAR reports the results of a number of eye irritation studies of different design.

Animal studies: A neutralised sodium chromate solution was not irritant to the rabbit eye. In contrast, repeated administration of potassium dichromate in powder form daily for 7 days caused severe irritation including necrosis of the conjunctivae and ulceration of the cornea

Occupational exposure: Accidental splashing of highly water-soluble Cr(VI) compounds in solution into the eye has resulted in damage to the human eye. A number of case reports have detailed both inflammation of the cornea and conjunctivae and in more severe cases, corneal erosion and ulceration. The severity of response is increased by low pH or high temperature. Accidental eye contact with the corrosive aqueous chromium (VI) trioxide results in

conjunctival congestion and necrosis and corneal oedema and opacity.

Justification for classification or non-classification

The results of a screening studies in the rabbit in vivo clearly show that chromic acid (aqueous chromium trioxide) is corrosive. Further testing in vivo for skin and eye irritation is therefore not required and cannot be justified on animal welfare grounds.

Chromium (VI) trioxide is listed in Annex VI to Regulation (EC) No 1272/2008 under Index No 024-001-00-0 with the following harmonised classification:

Skin Corr. 1A, H314 'Causes severe skin burns and eye damage'

No change to this classification is proposed.